Sexually transmitted infections in HIV-infected people in Switzerland: cross-sectional study.

Sexually transmitted infections (STI) in HIV-infected people are of increasing concern. We estimated STI prevalence and sexual healthcare seeking behaviour in 224 sexually active HIV-infected people, including men who have sex with men (MSM, n = 112), heterosexual men (n = 65) and women (n = 47). Laboratory-diagnosed bacterial STI were more common in MSM (Chlamydia trachomatis 10.7%; 95% CI 6.2, 18.0%, lymphogranuloma venereum 0.9%; 95% CI 0.1, 6.2%, Neisseria gonorrhoeae 2.7%; 95% CI 0.9, 8.0%, syphilis seroconversion 5.4%; 95% CI 2.0, 11.3%) than heterosexual men (gonorrhoea 1.5%; 95% CI 0.2, 10.3%) or women (no acute infections). Combined rates of laboratory-diagnosed and self-reported bacterial STI in the year before the study were: MSM (27.7%; 95% CI 21.1, 36.7%); heterosexual men (1.5%; 95% CI 0.2, 10.3%); and women (6.4%; 95% CI 2.1, 21.0%). Antibodies to hepatitis C virus were least common in MSM. Antibodies to herpes simplex type 2 virus were least common in heterosexual men. Most MSM, but not heterosexual men or women, agreed that STI testing should be offered every year. In this study, combined rates of bacterial STI in MSM were high; a regular assessment of sexual health would allow those at risk of STI to be offered testing, treatment and partner management.

HDAC inhibitor valproic acid enhances tumor cell kill in adenovirus-HSVtk mediated suicide gene therapy in HNSCC xenograft mouse model

Safety, efficacy and enhanced transgene expression are the primary concerns while using any vector for gene therapy. One of the widely used vectors in clinical. trials is adenovirus which provides a safe way to deliver the therapeutic gene. However, adenovirus has poor transduction efficiency in vivo since most tumor cells express low coxsackie and adenovirus receptors. Similarly transgene expression remains low, possibly because of the chromatization of adenoviral genome upon infection in eukaryotic cells, an effect mediated by histone deacetylases (HDACs). Using a recombinant adenovirus (Ad-HSVtk) carrying the herpes simplex thymidine kinase (HSVtk) and GFP genes we demonstrate that HDAC inhibitor valproic acid can bring about an increase in CAR expression on host cells and thereby enhanced Ad-HSVtk infectivity. It also resulted in an increase in transgene (HSVtk and GFP) expression. This, in turn, resulted in increased cell kill of HNSCC cells, following ganciclovir treatment in vitro as well as in vivo in a xenograft nude mouse model.

Limbal stem cell deficiency:Concept, aetiology, clinical presentation, diagnosis and management

Defects in renewal and repair of ocular surface as a result of limbal stem cell deficiency are now known to cause varying ocular, surface morbidity including persistent photophobia, repeated and persistent surface breakdown and overt conjunctivalisation of the cornea. Ocular conditions with abnormalities of ocular surface repair include pterygium, limbal tumours, aniridia, severe scarring following burns, cicatricial pemphigoid and Stevens-Johnson Syndrome, sequelae of mustard gas exposure and Herpes simplex epithelial disease, radiation keratopathy, contact lens induced keratopathy, neuroparalytic keratitis and drug toxicity. Restoring ocular health in these eyes has traditionally been frustrating. An understanding of these intricate cell renewal and maintenance processes has spurred the evolution in recent years of new treatment methods for several blinding diseases of the anterior segment; many more exciting modalities are in the offing. However, there is inadequate awareness among ophthalmologists about the current principles of management of ocular surface disorders. The purpose of this article is to help elucidate the important principles and current treatment methods relevant to ocular surface disorders.

Corneal Allograft Rejection:Risk Factors, Diagnosis, Prevention, and Treatment

Recent advances in corneal graft technology, including donor tissue retrieval, storage and surgical techniques, have greatly improved the clinical outcome of corneal grafts. Despite these advances, immune mediated corneal graft rejection remains the single most important cause of corneal graft failure. Several host factors have been identified as conferring a "high risk" status to the host. These include: more than two quadrant vascularisation, with associated lymphatics, which augment the afferent and efferent arc of the immune response; herpes simplex keratitis; uveitis; silicone oil keratopathy; previous failed (rejected) grafts; "hot eyes"; young recipient age; and multiple surgical procedures at the time of grafting. Large grafts, by virtue of being closer to the host limbus, with its complement of vessels and antigen-presenting Langerhans cells, also are more susceptible to rejection. The diagnosis of graft rejection is entirely clinical and in its early stages the clinical signs could be subtle. Graft rejection is largely mediated by the major histocompatibility antigens, minor antigens and perhaps blood group ABO antigens and some cornea-specific antigens. Just as rejection is mediated by active immune mediated events, the lack of rejection (tolerance) is also sustained by active immune regulatory mechanisms. The anterior chamber associated immune deviation (ACAID) and probably, conjunctiva associated lymphoid tissue (CALT) induced mucosal tolerance, besides others, play an important role. Although graft rejection can lead to graft failure, most rejections can be readily controlled if appropriate management is commenced at the proper time. Topical steroids are the mainstay of graft rejection management. In the high-risk situations however, systemic steroids, and other immunosuppressive drugs such as cyclosporin and tacrolimus (FK506) are of proven benefit, both for treatment and prevention of rejection.

Phylogeographical analyses of shellfish viruses: inferring a geographical origin for ostreid herpesviruses OsHV-1 (Malacoherpesviridae)

Mortality episodes have regularly been affecting the shellfish industry throughout its history. Some of these mortalities, especially in the oyster industry, have been attributed to herpesviruses. Purification of viral particles and molecular characterization have led to the development of routine monitoring, as well as improved taxonomic classification. Ostreid herpesviruses (Malacoherpesviridae), mostly affecting Pacific oysters Crassostrea gigas, have been sporadically recorded in the French oyster industry since the early 1990s (OsHV-1 'reference'). From 2008, a new variant of ostreid herpesvirus (OsHV-1 mu Var) has emerged and seriously impacted oyster production in France and other European countries. Consequently, the presence of ostreid herpesviruses has been monitored in different oyster producing areas around the world. The present study compiles molecular data that are available from survey efforts and takes a biogeographical approach, in order to infer an origin for ostreid herpesviruses. The highest genotype diversity was found in East Asia, despite a lower survey effort in that area than in Europe. Genotype network analyses show that both populations of ostreid herpesviruses present in Europe (OsHV-1 'reference' and OsHV-1 mu Var) are closely related to genotypes recorded in Asia. Moreover, ostreid herpesviruses have been detected in wild and symptom-free populations of various Asian native Crassostrea species. In the rest of the world, ostreid herpesvirus genotypes were recorded from cultivated C. gigas, and mostly associated with mortality episodes. Results of this study are therefore highly suggestive of an Asian origin for these viruses, which can be pathogenic under farming conditions. It also highlights the risks of European stock improvements, by means of overseas shellfish imports.

Études structurales d’interactions protéine/protéine impliquées dans l’érythropoïèse

Le développement hématopoïétique est régulé par l’action combinée de facteurs de transcription lignée spécifiques et de la machinerie transcriptionnelle de base, permettant ainsi l’expression de gènes en temps et lieu appropriés. Les travaux présentés dans cette thèse portent sur l’étude structurale et fonctionnelle d’interactions décisives pour la régulation de l’expression de gènes et impliquant des domaines de transactivation (TAD). En effet, les interactions faisant intervenir les TAD d’activateurs permettent de réguler l’activation de la transcription de façon spécifique. La première étude présentée dans cette thèse relate l'identification et la caractérisation d'une nouvelle interaction entre deux facteurs de transcription : le facteur hématopoïétique GATA-1 et la protéine suppresseur de tumeur p53. En combinant des études in vitro par titrage calorimétrique en condition isotherme (ITC) et par spectroscopie RMN et des études in vivo, nous avons identifié et caractérisé cette nouvelle interaction. Il s'avère que le TAD de p53 et le domaine de liaison à l’ADN de GATA-1 sont les domaines minimaux requis pour la formation de ce complexe. L'inhibition de la voie p53 par GATA-1 s’est avérée être la conséquence majeure de cette interaction, permettant ainsi le maintien en vie des précurseurs érythrocytaires via l’inhibition de l’apoptose. Un deuxième type d’interaction a fait l’objet d’études : l’interaction entre divers TAD et la machinerie transcriptionnelle de base, plus spécifiquement avec le Facteur général de Transcription IIH (TFIIH). La structure des complexes constitués par la sous-unité Tfb1/p62 du facteur TFIIH en interaction avec le TAD viral de VP16 d’une part, et avec le TAD humain du facteur érythrocytaire « Erythroid Krüppel-like factor» (EKLF) d’autre part, ont été résolues par spectroscopie RMN. La structure du complexe Tfb1/VP16 a révélée que le mode de liaison de VP16 à Tfb1 est similaire au mode de liaison du TAD de p53 avec le même partenaire. En effet, les TAD de VP16 et de p53 forment tous deux une hélice α de 9 résidus en interaction avec Tfb1. En dépit de partager avec p53 et VP16 le même site de liaison sur Tfb1/p62, la structure RMN du complexe EKLF/Tfb1 démontre que le mode d’interaction de ce TAD se distingue du mode de liaison canonique des activeurs transcriptionnels. Etonnamment, EKLF adopte un mécanisme de liaison semblable au mécanisme de liaison du facteur général de transcription TFIIEα avec p62, leurs conformations demeurent étendues en interaction avec Tfb1/p62. En se basant sur nos données structurales, nous avons identifié un résidu dans le TAD d'EKLF décisif pour la formation du complexe EKLF/p62 : le Trp73. La mutation de cet acide aminé perturbe son interaction avec Tfb1PH/p62PH et réduit significativement l'activité transcriptionnelle d'EKLF dans les érythrocytes.

Agonist-induced endocytosis of rat somatostatin receptor 1

Somatostatin-receptor 1 (sst1) is an autoreceptor in the central nervous system that regulates the release of somatostatin. Sst1 is present intracellularly and at the cell surface. To investigate sst1 trafficking, rat sst1 tagged with epitope was expressed in rat insulinoma cells 1046-38 (RIN-1046-38) and tracked by antibody labeling. Confocal microscopic analysis revealed colocalization of intracellularly localized rat sst1-human simplex virus (HSV) with Rab5a-green fluorescent protein and Rab11a-green fluorescent protein, indicating the distribution of the receptor in endocytotic and recycling organelles. Somatostatin-14 induced internalization of cell surface receptors and reduction of binding sites on the cell surface. It also stimulated recruitment of intracellular sst1-HSV to the plasma membrane. Confocal analysis of sst1-HSV revealed that the receptor was initially transported within superficial vesicles. Prolonged stimulation of the cells with the peptide agonist induced intracellular accumulation of somatostatin-14. Because the number of cell surface binding sites did not change during prolonged stimulation, somatostatin-14 was internalized through a dynamic process of continuous endocytosis, recycling, and recruitment of intracellularly present sst1-HSV. Accumulated somatostatin-14 bypassed degradation via the endosomal-lysosomal route and was instead rapidly released as intact and biologically active somatostatin-14. Our results show for the first time that sst1 mediates a dynamic process of endocytosis, recycling, and re-endocytosis of its cognate ligand.

Evaluation of Staining Methods for Cytologic Diagnosis of Oral Lesions

ObjectiveTo compare the efficacy of Papanicolaou, hematoxylin-eosin (H-E), Leishman and periodic acid-Schiff (PAS) staining for Cytologic diagnosis of oral lesions.Study DesignPatients from the Discipline of Stomatology, Sao Jose dos Campos Dental School, from the wards of Hospital Heliopolis and from the dentistry outpatient clinic of the University Hospital, University of São Paulo Medical School, with the following diseases, were selected: erythematous candidiasis (n = 9), pseudomembranous candidiasis (n = 10), squamous cell carcinoma In = 19), herpes simplex (n = 8), paracoccidioidomycosis In = 8) and pemphigus vulgaris (n = 1).ResultsThe different staining methods were compared regarding the quality of definition of cytoplasmic and nuclear morphologic characteristics and the identification of bacteria, fungi, inflammatory cells and secretions. Papanicolaou and H-E staining were considered better methods. In cases of fungal infections, PAS staining is useful and should be applied as a complementary method.ConclusionWithin the limitations of this study, it can be concluded that the cytologic diagnosis of oral lesions along with different staining methods is a useful tool for oral diagnosis. (Acta Cytol 2008;52:697-701)

Oral health in renal transplant recipients administered cyclosporin A or tacrolimus

OBJECTIVE: the aim of this study was to determine the oral status of renal transplant recipients receiving cyclosporin A (CsA) or tacrolimus (FK-506) as immunosuppressant.SUBJECTS AND METHODS: A total of 88 renal transplant recipients receiving CsA (63 men and 25 women, mean age 51.4 years) and 67 receiving FK-506 (57 men and 10 women, mean age 33.5 years) were included in the study. Donor type, histocompatibility, cold ischemia time and prior delayed graft function were similar between the two groups. Demographics and pharmacological data were recorded for all subjects.RESULTS: the results demonstrated that CsA caused a greater number of oral diseases. A greater number of gingival overgrowth was present in patients treated with CsA. However, the combined use with calcium channel blockers increased the gingival overgrowth number. The occurrence of candida in saliva was observed in 80 renal recipients treated with CsA and 20 treated with FK-506. The presence of squamous oral carcinoma (n = 3) and herpes simplex (n = 10) was observed in patients treated with CsA. These alterations were not observed in renal recipients treated with FK-506.CONCLUSIONS: Renal recipients constitute a high-risk group for oral diseases, as they are immunocompromised. However, the FK-506 regime appears to ameliorate this effect, compared with CsA. Adequate pre- and post-transplant oral health care is recommended for these subjects, irrespective of the time interval for which the drug is administered.

Lesões do trato gastrointestinal na síndrome da imunodeficiência adquirida: estudo de 45 necrópsias consecutivas.

This study was designed to evaluate retrospectively the frequency and etiology of the gastrointestinal (GI) lesions in 45 consecutive necropsies of adult patients with Acquired Immunodeficiency Syndrome (AIDS). Gross descriptions and histological sections of the GI tract, from mouth to anus, were reviewed. The slides were H&E stained, and when necessary special stains and immunohistochemical methods were also employed. There were lesions in GI tract in 37 (82.3%) patients; the mouth was the segment most frequently involved (73.3% of the cases), followed by the colon (55.5%). Multiple lesions occurred in 17 (37.7%) cases. Cytomegalovirus caused colonic lesions in 35.7% of the cases. Candidiasis was observed in 26.6% mainly in the mouth and herpes simplex (8.8%) was the important agent of esophageal lesions. Oral hairy leukoplasia associated with HPV was found in 16 (35.5%) cases. Neoplasia was diagnosed in 7 (15.5%) cases: four Kaposi's sarcoma, two anal intramucosal carcinomas and one gastric lymphoma. Our data confirm the high frequency and variety of GI tract alterations in AIDS.

Avaliação da segurança e eficácia de novo preenchedor à base de ácido hialurônico no tratamento dos sulcos nasolabiais e contorno dos lábios

Introduction: The use of dermal filling techniques for soft tissue augmentation has greatly increased in recent years. Hyaluronic acid is one of the most used temporary dermal fillers in the treatment of facial wrinkles, furrows, and folds due to its effectiveness and safety. Objective: To evaluate the efficacy and safety of Perfectha®, a new hyaluronic acid filler, for nasolabial folds and lip correction. Methods: Open, multicenter study comprising 87 women. Efficacy was evaluated by the Global Aesthetic Improvement Scale and the Wrinkle Severity Rating Scale. Safety was evaluated through observation and the reporting of side effects. Results: One week after the injection of the filler, improvement in nasolabial folds and lips was observed in 86% and 89% of the women, respectively. Mild or moderate transient inflammatory reaction and ecchymoses occurred in 15% and 9% of patients, respectively, mainly in nasolabial folds. Two patients presented labial herpes simplex after treatment of the lips. The good results were maintained in 76% and 57% of women for nasolabial folds and in 72% and 45% of women for lips after 3 and 6 months, respectively. Conclusion: Perfectha® was effective and safe for these indications.

Epidemiological and oral manifestations of HIV-positive patients in a specialized service in Brazil

The purpose of this study was to evaluate the prevalence of oral lesions in HIV-positive patients attending the Specialized Service for Infectious-contagious Diseases and Parasitoses of the Health Secretariat of the State of Pará (URE-DIPE/SESPA), in the city of Belém, PA, Brazil. A total of 79 HIV-positive patients (53 males and 26 females) were examined. Clinical and epidemiological evaluations were done by correlating the lesions with gender, race, chronological age, risk behavior and prevailing immune status (CD4+ cells count). Lesion location and the presence of associated factors, such as alcohol use, smoking and denture wearing, were quantified individually for each type of lesion using a diagnostic pattern based on the clinical aspects. Approximately 47% of the patients (n=37) presented some type of oral lesion. Candidiasis (28%) and periodontal disease (28%) were the most common, followed by cervical-facial lymphadenopathy (17.5%). Other lesions observed were hairy leukoplakia, melanin hyperpigmentation, ulcerative stomatitis (aphthous), herpes simplex, frictional keratosis and pyogenic granuloma. This analysis presented some relevance as to the statistical data. Concerning CD4+ cells, most lesions manifested with the reduction of the CD count. There were a larger number of HIV-positive female heterosexual patients. Alcohol and/or smoking were strongly associated with the occurrence of hairy leukoplakia in these patients. Candidiasis and periodontal disease were the most common oro-regional clinical manifestations in the patients.

Descrição de outras doenças sexualmente transmissíveis em pessoas infectadas pelo vírus da imunodeficiência humana do tipo 1

Noventa pacientes soropositivos para o HIV-1 foram estudados, visando-se a descrição de manifestações clínicas e de marcadores de outras doenças sexualmente transmissíveis, assim como de fatores demográficos e comportamentais que possam estar relacionados com a infecção pelo HIV-1 e em pacientes com SIDA/AIDS. A maioria dos entrevistados (83,3%) foi do sexo masculino, apresentou a média de idade 31,4 anos (variando entre 18 e 60 anos) e a distribuição da renda familiar mensal mostrou que 79,5% tinham um ganho inferior a cinco salários mínimos. Pelos menos um tipo de droga, foi consumido por 51,1%, sendo que 20.7% usaram droga não medicamentosa de uso injetável. Destes, 94,4% referiram antecedentes de doenças sexualmente transmissíveis. A observação dos hábitos sexuais revelou que 41,6% eram bissexuais, 38,2% heterossexuais e 20,2% eram homossexuais. Cerca de 51,1% dos bissexuais usaram drogas injetáveis e todos referiram a prática de sexo anal e foram positivos para a presença de anticorpos para Chlamydia. A média de idade da primeira relação sexual com penetração foi de 14.7 anos, enquanto que a média de idade em que ocorreu a primeira doença sexualmente transmissível foi de 20.6 anos. A quase totalidade (95,5%) dos entrevistados tiveram múltiplos parceiros sexuais, antes do conhecimento da soropositividade para o HIV-1. Dentre os 90 soropositivos, 73,3% referiram antecedentes de doenças sexualmente transmissíveis. Destes, 82,2% referiram a presença de secreção uretraI, de sífilis e de herpes simples. No momento da avaliação, 36,6% (33/90) apresentaram secreção uretral, anal e/ou vaginal, lesão genital, anal, perianal e/ou adenopatia inguinal, assim discriminado: Secreção (51,1%), vesículas (18,1%), lesão verrucosa (18,1%), Adenopatias iguinais ( 18,1% ), úlceras ( 12,1 %) e pápulas (6% ). A reação do VDRL foi positiva em 13,7% (11/80), sendo que neste grupo, 90,9% referiram a prática do sexo anal e 81,8% revelaram antecedentes de DST. Cerca de 96,4% (81/84) apresentaram anticorpos para Chlamydia, sendo que 81,8% revelaram a prática do sexo anal e 72,8% relataram antecedentes de DST .

Isolamento viral e diagnóstico molecular de herpevírus canino

Pós-graduação em Medicina Veterinária - FMVZ

Opportunistic and Other Infections in HIV-Infected Children in Latin America Compared to a Similar Cohort in the United States

Opportunistic and other infections have declined since the introduction of highly active antiretroviral therapy (HAART) in developed countries but few studies have addressed the impact of HAART in HIV-infected children from developing countries. This study examines the prevalence and incidence of opportunistic and other infections in Latin America during the HAART era. Vertically HIV-infected children enrolled in a cohort study between 2002 and 2007 were followed for the occurrence of 29 targeted infections. Cross-sectional and longitudinal analyses were performed to calculate the prevalence of infections before enrollment and the incidence rates of opportunistic and other infections after enrollment. Comparisons were made with data from a U. S. cohort (PACTG 219C). Of the 731 vertically HIV-infected children 568 (78%) had at least one opportunistic or other infection prior to enrollment. The most prevalent infections were bacterial pneumonia, oral candidiasis, varicella, tuberculosis, herpes zoster, and Pneumocystis jiroveci pneumonia. After enrollment, the overall incidence was 23.5 per 100 person-years; the most common infections (per 100 person-years) were bacterial pneumonia (7.8), varicella (3.0), dermatophyte infections (2.9), herpes simplex (2.5), and herpes zoster (1.8). All of these incidence rates were higher than those reported in PACTG 219C. The types and relative distribution of infections among HIV-infected children in Latin America in this study are similar to those seen in the United States but the incidence rates are higher. Further research is necessary to determine the reasons for these higher rates.